Associative learning plays a key role in early development by providing a means for learning predictive relationships between events. The ontogeny of associative learning is thought to depend on developmental processes within the central nervous system. However, little information exists concerning the cellular mechanisms of associative learning during development. The proposed research project is designed to examine developmental changes in neuronal function that underlie the ontogeny of classically conditioned eyeblink responses in rats. The cerebellum is an essential component of the neural circuitry that mediates eyeblink conditioning in adult organisms and exhibits extensive morphological development during the first four postnatal weeks in rats. Preliminary studies showed that the eyeblink conditioned response (CR) also developed during the first four postnatal weeks in rats. Moreover, disrupting cerebellar maturation experimentally impaired the ontogeny of eyeblink conditioning. These data provided compelling evidence for a link between cerebellar maturation and the development of eyeblink conditioning. However, the ability to determine the specific changes in neural processes that underlie the development of the eyeblink CR requires a physiological analysis of learning-related neural plasticity within the cerebellum and brainstem. Three experimental approaches will be used for examining the relationship between neural maturation and the ontogeny of eyeblink conditioning. First, the experiments of Specific Aims 1 and 2 will use extracellular recording methods to examine ontogenetic changes in neuronal activity within various components of the eyeblink conditioning neural circuitry. Second, the experiments of Specific Aim 3 will determine whether electrical stimulation of either the conditioned or unconditioned stimulus neural pathways could be used to alter the time-course of the ontogeny of eyeblink conditioning. Third, the experiments of Specific Aim4 will evaluate developmental changes in the induction of neuronal plasticity in the cerebellum. This research will yield unique data concerning the specific changes in neuronal function that could underlie associative eyeblink conditioning. This work may also lead to the discovery of general principles concerning the relationship between neural and behavioral development, which could be applied to the analysis of other types of behavioral responses. In addition to the basic research goals of this project, the results of these studies may lead to a better understanding of the functional pathology associated with various developmental disorders that affect the nervous system including fetal alcohol syndrome, exposure to environmental neurotoxins, infantile autism, and Down's syndrome.